With the recent progress in molecular biology and gene technology, many new cancer-specific antigens have been identified. Many studies have demonstrated the role of HLA class I-restricted cytotoxic T lymphocytes (CTLs) in cancer specific-immunotherapies. We have also established HLA-A24- and A26-restricted and cancer-specific CTLs from a patient with squamous cell carcinoma of the esophagus. Using CTLs, we identified a new gene SART-1 by cDNA-expression cloning and some SART-1-derived cancer rejection peptides were also identified. Further more, using the same approach, we identified a cyclophilin B gene that encodes antigenic epitopes recognized by HLA-A24-restricted and tumor-specific CTLs. Now we are performing phase I trials using these peptide vaccines and have found an increase in CTL precursor frequency in some cases in an in vitro study. However, other recent studies have reported that many tumors escape from CTL recognition by downregulation of HLA class I expression. Moreover, most cancer cells produce a suppressor agents against the immune system. Therefore, we must resolve these major problems to produce successful cancer vaccine therapy soon.